Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes

Research output: Contribution to journalJournal articlepeer-review

Epidermal homeostasis is tightly controlled by a balancing act of self-renewal or terminal differentiation of proliferating basal keratinocytes. An increase in DNA content as a consequence of a mitotic block is a recognized mechanism underlying keratinocyte differentiation, but the molecular mechanisms involved in this process are not yet fully understood. Using cultured primary keratinocytes, here we report that the expression of the mammalian microtubule and kinetochore-associated protein Clasp2 is intimately associated with the basal proliferative makeup of keratinocytes, and its deficiency leads to premature differentiation. Clasp2-deficient keratinocytes exhibit increased centrosomal numbers and numerous mitotic alterations, including multipolar spindles and chromosomal misalignments that overall result in mitotic stress and a high DNA content. Such mitotic block prompts premature keratinocyte differentiation in a p53-dependent manner in the absence of cell death. Our findings reveal a new role for Clasp2 in governing keratinocyte undifferentiated features and highlight the presence of surveillance mechanisms that prevent cell cycle entry in cells that have alterations in the DNA content.

Original languageEnglish
JournalJournal of Cell Science
Volume130
Issue number4
Pages (from-to)683-688
Number of pages6
DOIs
Publication statusPublished - 2017
Externally publishedYes

    Research areas

  • Animals, Cell Differentiation, Cell Line, Transformed, Cells, Cultured, DNA Damage, Epidermis, Gene Knockdown Techniques, Humans, Keratinocytes, Mice, Inbred C57BL, Microtubule-Associated Proteins, Mitosis, Tumor Suppressor Protein p53, Journal Article, Research Support, Non-U.S. Gov't

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